DESCRIPTION: This proposal is designed to investigatethe mechanism of the release of AVP and ACTH and plasma renin activity in response to hemorrhage. The proposal addresses the relative contribution of atrial cardiac receptors and arterial baroreceptor in these responses as well as their interactions. The investigator found that blocking cardiac receptors with local anesthetics injected into the pericardial space of conscious dogs had no effect on vasopressin release whereas vasopressin release during hemorrhage was more tightly correlated to the decrease in arterial blood pressure. Based on these results he suggested that the atrial receptors are not involved in the release of AVP in hemorrhage or, at least, they are not the dominant influence; thereby challenging traditional concepts concerning the release of AVP. The investigator has devised techniques to expand these studies. These techniques make use of unanesthetized dog preparations in which the aortic baroreceptors as well as one carotid sinus are denervated, while the other carotid sinus can be isolated from the circulation by means of occluding devises and its pressure can be maintained constant. In addition, by means of occluding devises on the thoracic inferior vena cava, venous return can be regulated thereby controlling atrial pressure. Finally, the cardiac receptors can be eliminated by the injection of local anesthetics into the pericardial space. Using this preparation the relative contribution from the cardiac and arterial baroreceptors in the control of AVP, plasma renin and ACTH can be addressed. In addition, the interactions between these receptors can be evaluated. The specific aims of the proposal are: 1) to show that unloading cardiac receptors alone stimulates an increase in plasma renin activity but not an increase in AVP and ACTH in response to thoracic inferior vena cava occlusion; 2) To show that unloading arterial baroreceptor alone can stimulate increases in plasma AVP and ACTH similar to those obtained during systemic hypotension but that the plasma renin activity response is greater when both arterial and atrial receptors are unloaded; and, 3) to show that afferent signals from the heart chronically inhibit renin but not AVP and ACTH secretion in conscious normovolemic dogs.